CELLULAR MECHANISMS OF MUSCLE FATIGUE

Fitts, R H

Angol nyelvű Tudományos Összefoglaló cikk (Folyóiratcikk)
Megjelent: PHYSIOLOGICAL REVIEWS 0031-9333 1522-1210 74 (1) pp. 49-94 1994
    Azonosítók
    Fatigue, defined as the failure to maintain the required or expected power output, is a complex problem, since multiple factors are clearly involved, with the relative importance of each dependent on the fiber type composition of the contracting muscle(s), and the intensity, type, and duration of the contractile activity. The primary sites of fatigue appear to be within the muscle cell itself and for the most part do not involve the central nervous system or the neuromuscular junction. The major hypotheses of fatigue center on disturbances in the surface membrane, E-C coupling, or metabolic events. The cell sites most frequently linked to the etiology of skeletal muscle fatigue are shown in Figure 1. Skeletal muscles are composed of at least four distinct fiber types (3 fast twitch and 1 slow twitch), with the slow type I and fast type IIa fibers containing the highest mitochondrial content and fatigue resistance. Despite fiber type differences in the degree of fatigability, the contractile properties undergo characteristic changes with the development of fatigue that can be observed in whole muscles, single motor units, and single fibers. The P(o) declines, and the contraction and relaxation times are prolonged. Additionally, there is a decrease in the peak rate of tension development and decline and a reduced V(o). Changes in V(o) are more resistant to fatigue than P(o) and are not observed until P(o) has declined by at least 10% of its initial prefatigued value. However, the reduced peak power by which fatigue is defined results from both a reduction in V(o) and P(o). In the absence of muscle fiber damage, the prolonged relaxation time associated with fatigue causes the force-frequency curve to shift to the left, such that peak tensions are obtained at lower frequencies of stimulation. In a mechanism not clearly understood, the central nervous system senses this condition and reduces the α-motor nerve activation frequency as fatigue develops. In some cases, selective LFF develops that displaces the force-frequency curve to the right. Although not proven, it appears likely that this condition is associated with and likely caused by muscle injury, such that the SR releases less Ca2+ at low frequencies of activation. Alternatively, LFF could result from a reduced membrane excitability, such that the sarcolemma action potential frequency is considerably less than the stimulation frequency. Fatigue-induced disturbances in E-C coupling could be mediated by an altered sarcolemma or T tubular excitability, a depressed T tubular charge sensor, inhibition of the SR Ca2+ release channel, or an uncoupling of the T tubular charge sensor and the SR Ca2+ release channel. The membrane hypothesis of muscle fatigue states that the sarcolemma Na+-K+ pump is unable to maintain the ionic gradients for K+ and Na+ essential for the maintenance of the V(m) and cell excitability. The increased [K+](o), decreased [K+](i), and elevated K+ conductance are all thought to contribute to the depolarized V(m) frequently observed in fatigued muscle cells. The greatest depolarization occurs in centrally located fibers, and the effect is likely to be largest in T tubular regions located furthest from the sarcolemma. Consequently, the interior regions of the T tubules may depolarize enough to produce block of the action potential, which in turn would produce inactivation of the centrally located myofibrils. It seems unlikely that fatigue could be mediated by a simple drop in the amplitude of the action potential, since the reduced spike height is insufficient to elicit inactivation. Furthermore, changes in the action potential amplitude do not show a good temporal relationship with the change in force. Because the ionic gradients are rapidly reestablished following exercise, it is clear that the membrane hypothesis cannot contribute to the slow recovery phase of muscle fatigue.
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    2021-05-09 02:49